Urologic chronic pelvic pain syndromes (UCPPS) debilitate millions of patients in the U.S., yet the etiologies are unknown, and no effective therapies or diagnostic markers exist. Interstitial cystitis/bladder pain syndrome (IC/BPS or IC) primarily afflicts women with severe pelvic pain, voiding dysfunction, and depression, and men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are similarly afflicted. Many potential UCPPS mechanisms have been studied—including infection, inflammation, neurogenic dysfunction, and hypothalamic-pituitary-adrenal (HPA) axis dysregulation—but no mechanism associates with more than a subset of patients.